Journal of Molecular Modeling

, Volume 19, Issue 3, pp 1179–1194 | Cite as

In vitro inhibitory profile of NDGA against AChE and its in silico structural modifications based on ADME profile

  • Chandran Remya
  • Kalarickal Vijayan Dileep
  • Ignatius Tintu
  • Elessery Jayadevi Variyar
  • Chittalakkottu Sadasivan
Original Paper

Abstract

Acetylcholinesterase (AChE) inhibitors are currently in focus for the pharmacotherapy of Alzheimer’s disease (AD). These inhibitors increase the level of acetylcholine in the brain and facilitate cholinergic neurotransmission. AChE inhibitors such as rivastigmine, galantamine, physostigmine and huperzine are obtained from plants, indicating that plants can serve as a potential source for novel AChE inhibitors. We have performed a virtual screening of diverse natural products with distinct chemical structure against AChE. NDGA was one among the top scored compounds and was selected for enzyme kinetic studies. The IC50 of NDGA on AChE was 46.2 μM. However, NDGA showed very poor central nervous system (CNS) activity and blood–brain barrier (BBB) penetration. In silico structural modification on NDGA was carried out in order to obtain derivatives with better CNS activity as well as BBB penetration. The studies revealed that some of the designed compounds can be used as lead molecules for the development of drugs against AD

Figure

Inhibitory activity of NDGA against AChE

Keywords

Acetylcholinesterase NDGA ADME CNS activity Induced fit docking 

Notes

Acknowledgments

The authors gratefully acknowledge the use of computational facilities provided by Bioinformatics Infrastructure Facility (supported by DBT, Government of India) at Kannur University and BIOGENE cluster, Bioinformatics Resources and Application Facility at C-DAC (Center for Development of Advanced Computing) Pune, India.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Chandran Remya
    • 1
  • Kalarickal Vijayan Dileep
    • 1
  • Ignatius Tintu
    • 1
  • Elessery Jayadevi Variyar
    • 1
  • Chittalakkottu Sadasivan
    • 1
  1. 1.Department of Biotechnology and Microbiology and Inter University Centre for BiosciencesKannur UniversityKeralaIndia

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